A 6-amino-acid synthetic peptide and the most potent growth hormone releasing peptide ever developed. Produces the largest GH release of any GHRP. Uniquely, hexarelin also binds to cardiac CD36 receptors, providing GH-independent cardioprotective effects that have generated significant research interest.
Hexarelin (His-D-2-MeTrp-Ala-Trp-D-Phe-Lys-NH2), also known as examorelin, is the most potent synthetic growth hormone releasing peptide. It produces greater GH release per dose than GHRP-6, GHRP-2, or ipamorelin.
What makes hexarelin unique among GHRPs is its binding to CD36 receptors in cardiac tissue — an interaction independent of the ghrelin receptor. This CD36 binding provides cardioprotective effects (anti-fibrotic, anti-apoptotic in cardiomyocytes) that persist even after GH receptor desensitization occurs.
Hexarelin's dual receptor mechanism distinguishes it from all other GHRPs. The GHS-R1a interaction produces the most potent GH release of any secretagogue, but this same potency leads to receptor desensitization with repeated dosing (GH response diminishes over 4-8 weeks). The CD36 interaction does not desensitize, providing sustained cardioprotective effects even when GH release has attenuated.
| Pathway | Effect | Significance |
|---|---|---|
| Maximum GH release | Most potent GHS-R1a agonist known | Greatest peak GH levels of any GHRP |
| CD36 cardiac binding | Activates cardioprotective pathways independent of GH | Anti-fibrotic, anti-apoptotic effects on cardiomyocytes |
| GHS-R1a desensitization | Receptor downregulation with chronic high-potency stimulation | GH-releasing effect diminishes over 4-8 weeks of continuous use |
| Cortisol/prolactin | Significant HPA axis stimulation | Comparable to GHRP-6; less selective than ipamorelin or GHRP-2 |
| Anti-fibrotic | Reduces cardiac fibrosis via CD36-PPARgamma pathway | May benefit heart failure and post-MI remodeling |
| Study | Design | Findings | Level |
|---|---|---|---|
| GH potency | Clinical comparison | Hexarelin produced greater GH area-under-curve than GHRP-6, GHRP-2, and ipamorelin at equivalent doses | Level II |
| Cardiac protection | Preclinical + Phase II | Improved cardiac function in animal MI models. Human Phase II showed improved cardiac parameters in GH-deficient patients. | Level II |
| CD36 mechanism | In vitro + in vivo | Cardioprotective effects persisted even when GHS-R1a was blocked, confirming CD36-dependent mechanism | Preclinical |
| Desensitization | Clinical observation | GH release diminished by 50-70% after 4-8 weeks of daily hexarelin administration | Level II |
Desensitization: The main limitation. GH-releasing effect diminishes with chronic use, making it less suitable for long-term GH optimization.
Cortisol and prolactin: Similar profile to GHRP-6. Significant elevations with chronic use.
Appetite stimulation: Present, similar to GHRP-6.
| Jurisdiction | Status |
|---|---|
| FDA | Not approved |
| WADA | Banned under S2 |
| Research | Primarily of interest for cardiac applications (CD36 pathway) rather than GH optimization |